Pregnancy associated plasma protein A2 (PAPP-A2) affects bone size and shape and contributes to natural variation in postnatal growth in mice.
Pregnancy associated plasma protein A2 (PAPP-A2) affects bone size and shape and contributes to natural variation in postnatal growth in mice.
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DOI：
10.1371/journal.pone.0056260
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fung SH
中科院分区：
文献类型：
--
作者：
Christians JK;de Zwaan DR;Fung SH
妊娠相关血浆蛋白A2（PAPP-A2）是胰岛素样生长因子结合蛋白5的一种蛋白酶，因其在妊娠和产后发育中的作用而受到越来越多的关注。本研究的目的是表征PAPP-A2缺失对10周龄小鼠骨大小和形状的影响，并确定Pappa 2是否是先前确定的数量性状位点（QTL）的基因，该基因有助于小鼠出生后生长的自然变异。组成型PAPP-A2缺失纯合子小鼠比野生型同窝小鼠轻，下颌骨尺寸较小，颅骨、肱骨、股骨、胫骨、骨盆带和尾骨较短。此外，由于对体重的影响，PAPP-A2缺失降低了下颌骨尺寸和颅骨、股骨、骨盆带和尾骨的长度，这比预期的要多。除了对骨骼大小的影响外，PAPP-A2缺乏还改变了下颌骨和骨盆带的形状，如几何形态测量学所评估的。PAPP-A2缺失的纯合子小鼠下颌骨较浅，骨盆带形状更女性化。使用定量互补测试，我们证实，Pappa 2是负责先前确定的QTL的影响，表明Pappa 2基因的自然变异有助于小鼠出生后生长的变化。如果Pappa 2基因的类似功能变异存在于其他物种中，这种变异对骨盆带形状的影响可能解释先前报道的Pappa 2 SNP与人类髋关节发育不良和牛分娩之间的关联。
Pregnancy associated plasma protein A2 (PAPP-A2) is a protease of insulin-like growth factor binding protein 5 and is receiving increasing attention for its roles in pregnancy and postnatal growth. The goals of the present study were to characterize the effects of PAPP-A2 deletion on bone size and shape in mice at 10 weeks of age, and to determine whether Pappa2 is the gene responsible for a previously-identified quantitative trait locus (QTL) contributing to natural variation in postnatal growth in mice. Mice homozygous for constitutive PAPP-A2 deletion were lighter than wild-type littermates, and had smaller mandible dimensions and shorter skull, humerus, femur, tibia, pelvic girdle, and tail bone. Furthermore, PAPP-A2 deletion reduced mandible dimensions and the lengths of the skull, femur, pelvic girdle, and tail bone more than would be expected due to the effect on body mass. In addition to its effects on bone size, PAPP-A2 deficiency also altered the shape of the mandible and pelvic girdle, as assessed by geometric morphometrics. Mice homozygous for the PAPP-A2 deletion had less deep mandibles, and pelvic girdles with a more feminine shape. Using a quantitative complementation test, we confirmed that Pappa2 is responsible for the effects of the previously-identified QTL, demonstrating that natural variation in the Pappa2 gene contributes to variation in postnatal growth in mice. If similar functional variation in the Pappa2 gene exists in other species, effects of this variation on the shape of the pelvic girdle might explain the previously-reported associations between Pappa2 SNPs and developmental dysplasia of the hip in humans, and birthing in cattle.
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DOI：
10.1152/ajpendo.00648.2007
发表时间：
2008-01-01
影响因子：
5.1
作者：
Conover, Cheryl A.
通讯作者：
Conover, Cheryl A.
影响因子：
3.3
作者：
Luna-Nevarez, P.;Rincon, G.;Thomas, M. G.
通讯作者：
Thomas, M. G.
影响因子：
4.8
作者：
Conover, Cheryl A.;Boldt, Henning B.;Powell, David R.
通讯作者：
Powell, David R.
影响因子：
5.8
作者：
Chen, BK;Leiferman, KM;Conover, CA
通讯作者：
Conover, CA
影响因子：
2.5
作者：
Christians, JK;Keightley, PD
通讯作者：
Keightley, PD